ESPE Abstracts

Background: Frasier syndrome (FS) is a rare inherited disease characterized by gonadal dysgenesis and progressive nephropathy, resulting from mutations in intron 9 splice donor site of the Wilms’ tumor suppressor gene 1 (WT1). It can be associated with 46,XY gonadal dysgenesis (female external genitalia with a 46,XY karyotype). Gonadoblastoma usually occurs in the second decade of life but can develop as early as 9 months of age in children with gonadal dysgenesis. Here, we present a child of FS, and associated 46,XY gonadal dysgenesis diagnosed during etiologic screening of progressive nephropathy.

Case report: An 8-year-old girl was evaluated for edema and massive proteinuria. Laboratory studies indicated nephrotic syndrome (NS): hypoalbuminemia, hyperlipidemia, and massive proteinuria without hematuria. She did not respond to prednisolone treatment. She underwent a renal biopsy, and the pathology revealed focal segmental glomerulosclerosis (FSGS). Genetic screening testing for NS etiology was performed. A heterozygous variant (NM_024426.6: c.1447+4C>T) was detected in intron 9 of the WT1 gene. She patient was diagnosed with FS. The chromosomal karyotype analysis of the patient, who was raised as a girl, was found 46,XY. Physical examination revealed a female external genitalia of the non-dysmorphic patient. Her weight was 40.5 kg (2,8 SDS), height 134.9 cm (1,5 SDS), and BMI was 22.3 kg/m2 (2,3 SDS). Laboratory evaluation revealed primary gonadal failure with FSH: 30.7 mIU/mL, LH: 1.5 mIU/mL, total testosterone: 5 ng/dL, normal tumor markers and other hormonal parameters. Pelvic ultrasonography showed müllerian structures (uterus, streak gonads; a hyperechoic appearance measuring 28 × 6 × 10 mm in the right adnexal region and 22 × 8 × 5 mm in the left adnexal region). Pelvic MRI revealed hypointense soft tissue in this area on T2-weighted imaging, which was considered to be consistent with streak/fibrotic gonads. The diagnosis of 46,XY gonadal dysgenesis was confirmed. Streak gonads are planned to be removed as soon as possible.

Conclusion: Genetic screening for WT1 mutations in children with steroid-resistant nephrotic syndrome may allow early diagnosis of FS and thus early gonadectomy in the patients with 46,XY gonadal dysgenesis and potential prevention of gonadal tumor occurrence.

Keywords: Frasier syndrome, nephrotic syndrome, focal segmental glomerulosclerosis, gonadal dysgenesis, WT1 gene, 46XY DSD, Wilms tumor, gonadoblastoma.